Genital herpes, caused by infection with herpes simplex virus type 2 (HSV-2), is the most common sexually transmitted disease in humans. The current prevalence of HSV-2 infections is greater than 20% among adults in the United States (Ashley and Wald, Clin. Microbiol. Rev. 12:1-8, 1999). This disease is a major concern in public health due to its morbidity, frequency of recurrence, and life-threatening severity in the case of newborns infected with the virus following intrapartum transmission.
The serological diagnosis for HSV-2 infection has been hampered, however, by the fact that there exists extensive cross-reactivity of HSV-2 antibodies to herpes simplex virus type 1 (HSV-1). The two subtypes of HSV have important differences in epidemiology and natural history: HSV-1 usually causes orolabial disease, whereas HSV-2 almost always leads to genital disease. For a general review of HSV epidemiology and diagnosis, see Brugha et al., Int. J. Epidemiol. 26:698-709, 1997; Ashley and Wald, supra.
Various approaches have been developed in an effort to identify HSV-2 specific antibodies. The most reliable method for a type-specific detection of HSV-2 antibodies to date is an immunoblot assay, preferably a Western blot assay. The significant drawback of this method is that the procedure is labor-intensive and requires the investigator to have a certain level of skill in order to achieve unequivocal results. In the last decade or so, several HSV glycoproteins have been identified as the viral proteins that contain type-specific epitopes. Immunoassays have been developed based on these glycoproteins for type-specific determination of HSV-2 infection. See, e.g., Lee et al., J. Clin. Microbiol. 22:641-644 (1985); Eis-Hubinger et al., J. Clin. Microbiol. 37:1242-1246 (1999); Groen et al., J. Clin. Microbiol. 36:845-847 (1998); Ashley et al., J. Clin. Microbiol. 36:294-295 (1998); Hashido et al., J. Med. Virol. 53:319-323 (1997); and U.S. Pat. No. 4,764,459.
As these methods show a varying degree of sensitivity and specificity, there is one common problem associated with these glycoprotein-based immunoassays for HSV-2 antibody type-specific detection. The full length glycoproteins are obtained through isolation of either naturally-occurring viral proteins or recombinantly expressed proteins. These procedures can be costly and susceptible to impurities and thus cross-reactivity.
Studies have indicated that peptides corresponding to partial sequences of certain viral proteins of HSV-2 may be useful in HSV-2 type-specific detection, as these peptides may represent some HSV-2 type-specific epitopes. See, e.g., Levi et al., Clin. Diagn. Lab. Immunol. 3:265-269 (1996); Ackermnann et al., J. Med. Virol. 55:281-287 (1998); Marsden et al., J. Med. Virol. 56:79-84 (1998); Lijeqvist et al., J Gen. Virol 79:1215-1224 (1998); Grabowska et al., J. Gen. Virol. 80:1789-1798 (1999); U.S. Patent Nos. 5,919,616 and 5,965,357. The present invention provides novel peptide sequences of HSV-2 glycoprotein G2 that can be used in HSV-2 type-specific diagnosis.
All items of published literature and patents cited in the specification are hereby incorporated herein by reference.